Sterol biosensor reveals LAM-family Ltc1-dependent sterol flow to endosomes upon Arp2/3 inhibition
Sterol biosensor reveals LAM-family Ltc1-dependent sterol flow to endosomes upon Arp2/3 inhibition
Sterols are crucial components of biological membranes, which are synthetized in the ER and accumulate in the plasma membrane (PM). Here, by applying a genetically encoded sterol biosensor (D4H), we visualize a sterol flow between PM and endosomes in the fission yeast Schizosaccharomyces pombe. Using time-lapse and correlative light-electron microscopy, we found that inhibition of Arp2/3-dependent F-actin assembly promotes the reversible relocalization of D4H from the PM to internal sterol-rich compartments (STRIC) labeled by synaptobrevin Syb1. Retrograde sterol internalization to STRIC is independent of endocytosis or an intact Golgi, but depends on Ltc1, a LAM/StARkin-family protein localized to ER-PM contact sites. The PM in ltc1Δ cells over-accumulates sterols and upon Arp2/3 inhibition forms extended ER-interacting invaginations, indicating that sterol transfer contributes to PM size homeostasis. Anterograde sterol movement from STRIC is independent of canonical vesicular trafficking but requires Arp2/3, suggesting a novel role for this complex. Thus, transfer routes orthogonal to vesicular trafficking govern the flow of sterols in the cell.
- University of Lausanne Switzerland
- University of Geneva Switzerland
Cell Membrane, Golgi Apparatus, Biosensing Techniques, Endosomes, Endoplasmic Reticulum, Article, Actin-Related Protein 2-3 Complex, Actins, Antiporters, Endocytosis, Mixed Function Oxygenases, R-SNARE Proteins, Sterols, Actin-Related Protein 2-3 Complex/antagonists & inhibitors; Actin-Related Protein 2-3 Complex/metabolism; Actins/metabolism; Antiporters/genetics; Antiporters/metabolism; Biosensing Techniques; Cell Membrane/drug effects; Cell Membrane/genetics; Cell Membrane/metabolism; Endocytosis/drug effects; Endocytosis/genetics; Endoplasmic Reticulum/genetics; Endoplasmic Reticulum/metabolism; Endosomes/drug effects; Endosomes/metabolism; Endosomes/ultrastructure; Genes, Reporter; Golgi Apparatus/metabolism; Microscopy, Electron, Transmission; Mixed Function Oxygenases/genetics; Mixed Function Oxygenases/metabolism; Mutation; R-SNARE Proteins/metabolism; Schizosaccharomyces/metabolism; Sterols/metabolism, Microscopy, Electron, Transmission, Genes, Reporter, Mutation, Schizosaccharomyces
Cell Membrane, Golgi Apparatus, Biosensing Techniques, Endosomes, Endoplasmic Reticulum, Article, Actin-Related Protein 2-3 Complex, Actins, Antiporters, Endocytosis, Mixed Function Oxygenases, R-SNARE Proteins, Sterols, Actin-Related Protein 2-3 Complex/antagonists & inhibitors; Actin-Related Protein 2-3 Complex/metabolism; Actins/metabolism; Antiporters/genetics; Antiporters/metabolism; Biosensing Techniques; Cell Membrane/drug effects; Cell Membrane/genetics; Cell Membrane/metabolism; Endocytosis/drug effects; Endocytosis/genetics; Endoplasmic Reticulum/genetics; Endoplasmic Reticulum/metabolism; Endosomes/drug effects; Endosomes/metabolism; Endosomes/ultrastructure; Genes, Reporter; Golgi Apparatus/metabolism; Microscopy, Electron, Transmission; Mixed Function Oxygenases/genetics; Mixed Function Oxygenases/metabolism; Mutation; R-SNARE Proteins/metabolism; Schizosaccharomyces/metabolism; Sterols/metabolism, Microscopy, Electron, Transmission, Genes, Reporter, Mutation, Schizosaccharomyces
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